Related Experiment Video
Updated: Jun 16, 2026
07:06
A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Coordination-Driven Direct C─H Metalation of N-Heterocycles With a Superbasic Co(II) Amide Co(TMP)2.
Na Jin1, Manting Mu2, Max García-Melchor2,3,4
1Departement Für Chemie, Biochemie und Pharmazie, Universität Bern, 3012 Bern, Switzerland.
Angewandte Chemie (International Ed. in English)
|June 15, 2026
Summary
A new cobalt(II) amide, Co(TMP)2, enables efficient and regioselective C─H metalation of N-heterocycles. This versatile reagent facilitates direct functionalization, overcoming challenges with conventional bases.
Area of Science:
- Organometallic Chemistry
- Organic Synthesis
- Heterocyclic Chemistry
Background:
- Metalation of N-heterocycles is difficult due to poor C─H bond activation and unstable intermediates.
- Conventional alkali metal bases have limitations in functionalizing these compounds.
Purpose of the Study:
- To develop a novel method for high-yielding and regioselective C─H metalation of N-heterocycles.
- To explore the utility of a superbasic cobalt(II) amide, Co(TMP)2, as a versatile reagent.
Main Methods:
- Utilized cobalt(II) amide, Co(TMP)2 (TMP = 2,2,6,6-tetramethylpiperidide), for C─H metalation via Co(II)-H exchange.
- Employed NMR reaction monitoring, isolation of intermediates, and DFT calculations to understand regioselectivity.
- Investigated controlled di-cobaltation of pyrimidine and pyrazine.
Main Results:
- Achieved high-yielding and regioselective C─H metalation of diverse N-heterocycles.
- Demonstrated controlled di-cobaltation of pyrimidine and pyrazine.
- Established that coordination effects, not just C─H acidity, dictate regioselectivity.
- Successfully synthesized sterically demanding TMP-substituted heterocycles via oxidative coupling.
Conclusions:
- Co(TMP)2 is a mechanistically distinct and versatile reagent for N-heterocycle functionalization.
- The method offers a powerful alternative to conventional metalation strategies.
- Provides new routes for synthesizing complex heterocyclic compounds.
More Related Videos
Related Concept Videos
02:54Coordination Compounds and Nomenclature
In most main group element compounds, the valence electrons of the isolated atoms combine to form chemical bonds that satisfy the octet rule. For instance, the four valence electrons of carbon overlap with electrons from four hydrogen atoms to form CH4. The one valence electron leaves sodium and adds to the seven valence electrons of chlorine to form the ionic formula unit NaCl (Figure 1a). Transition metals do not normally bond in this fashion. They primarily form coordinate covalent bonds, a...
02:51Metal-Ligand Bonds
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
01:23Properties of Organometallic Compounds
Organometallic compounds are compounds that contain a carbon–metal bond. Carbon belongs to an organyl group like alkyl, aryl, allyl, or benzyl groups. The metal can be from Group I or Group II of the periodic table, a transition metal, or a semimetal.
01:17Reactions of α-Halocarbonyl Compounds: Nucleophilic Substitution
Nucleophilic substitution in α-halocarbonyl compounds can be achieved via an SN2 pathway. The reaction in α-haloketones is generally carried out with less basic nucleophiles. The use of strong basic nucleophiles leads to the generation of α-haloenolate ions, which often participate in other side reactions.
02:34Structural Isomerism
Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can be...
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can be...
01:11ortho–para-Directing Activators: –CH3, –OH, –NH2, –OCH3
All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...